Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 21, 2017; 23(7): 1203-1214
Published online Feb 21, 2017. doi: 10.3748/wjg.v23.i7.1203
Caffeic acid phenethyl ester up-regulates antioxidant levels in hepatic stellate cell line T6 via an Nrf2-mediated mitogen activated protein kinases pathway
Ning Yang, Juan-Juan Shi, Feng-Ping Wu, Mei Li, Xin Zhang, Ya-Ping Li, Song Zhai, Xiao-Li Jia, Shuang-Suo Dang
Ning Yang, Juan-Juan Shi, Feng-Ping Wu, Mei Li, Xin Zhang, Ya-Ping Li, Song Zhai, Xiao-Li Jia, Shuang-Suo Dang, Department of Infectious Diseases, the Second Affiliated Hospital of Medical School of Xi’an Jiaotong University, Xi’an 710004, Shannxi Province, China
Author contributions: Yang N and Dang SS designed the research; Yang N, Shi JJ, Wu FP, Li M, Zhang X and Li YP performed the research; Yang N, Zhai S and Jia XL analyzed the data; and Yang N and Shi JJ wrote the paper.
Supported by the Liver Fibrosis Foundation of Wang Bao-En of China, No. 20100033; and the Science and Technology Foundation of Shaanxi Province of China, No. 2010K01-199.
Institutional review board statement: No human or animal subjects were used in this study.
Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Shuang-Suo Dang, PhD, MD, Department of Infectious Diseases, the Second Affiliated Hospital of Medical School of Xi’an Jiaotong University, No. 157 Xi’wu Road, Xi’an 710004, Shaanxi Province, China. dang212@126.com
Telephone: +86-29-87679688 Fax: +86-29-87679688
Received: November 15, 2016
Peer-review started: November 15, 2016
First decision: December 19, 2016
Revised: December 27, 2016
Accepted: January 11, 2017
Article in press: January 11, 2017
Published online: February 21, 2017
Processing time: 97 Days and 3.1 Hours
Abstract
AIM

To investigate the antioxidant effect of caffeic acid phenethyl ester (CAPE) in hepatic stellate cell-T6 (HSC-T6) cells cultured in vitro and the potential mechanisms.

METHODS

HSC-T6 cells were cultured in vitro and treated with various concentrations of CAPE for 24, 48 and 72 h, respectively. Cell proliferation was investigated using the MTT assay, and cell ultrastructural alterations were observed by transmission electron microscopy. Flow cytometry was employed to investigate the effects of CAPE on apoptosis and the levels of reactive oxygen species in HSC-T6 cells cultured in vitro. An enzyme immunoassay instrument was used to evaluate antioxidant enzyme expression. The effect on α-smooth muscle actin was shown using immunofluorescence. Gene and protein levels of Nrf2, related factors, and mitogen activated protein kinases (MAPKs), in HSC-T6 cells were detected using RT-PCR and Western blot, respectively.

RESULTS

CAPE inhibited the proliferation and activation of HSC-T6 cells cultured in vitro. CAPE increased the antioxidant levels and the translocation of Nrf2 from the cytoplasm to the nucleus in HSC-T6 cells. Moreover, the phosphorylation of MAPKs in cells decreased in response to CAPE. Interestingly, CAPE-induced oxidative stress in the cells was significantly attenuated by pretreatment with MAPKs inhibitors.

CONCLUSION

CAPE inhibits cell proliferation and up-regulates the antioxidant levels in HSC-T6 cells partly through the Nrf2-MAPKs signaling pathway.

Keywords: Caffeic acid phenethyl ester; Liver fibrosis; Antioxidation; Nrf2; Mitogen activated protein kinases

Core tip: Liver fibrosis is a pathological response to hepatocyte injury, including oxidative stress, which is a primary mechanism of liver damage. Caffeic acid phenethyl ester (CAPE) is a phenolic compound extracted from honeybee propolis that has strong biological properties in liver protection and as an antioxidant and anti-fibrosis agent. It has been used in the treatment of several diseases. In this study, we investigated the antioxidant effect of CAPE in HSC-T6 cells and its potential mechanism. Our results demonstrated that CAPE inhibited cell proliferation and up-regulated the antioxidant levels in HSC-T6 cells partly through the Nrf2-MAPKs signaling pathway.